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フェリチンの鉄酸化・ミネラル化に関する研究
http://hdl.handle.net/10911/00040962
http://hdl.handle.net/10911/00040962e7b6fdd6-a295-484f-90df-0383b4547d54
| 名前 / ファイル | ライセンス | アクション |
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rikogakukenkyuka_Takumi-Kuwata(sinsa).pdf (1.8 MB)
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rikogakukenkyuka_Takumi-Kuwata(yosi).pdf (524.5 kB)
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rikogakukenkyuka_Takumi-Kuwata(zen).pdf (4.3 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2023-03-23 | |||||
| タイトル | ||||||
| タイトル | フェリチンの鉄酸化・ミネラル化に関する研究 | |||||
| 言語 | ja | |||||
| タイトル | ||||||
| タイトル | Studies on the iron oxidation/mineralization of ferritin | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | jpn | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Ferritin | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Iron core formation | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Phosphate | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Neuroferritinopathy | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 著者 |
桑田, 巧
× 桑田, 巧× Kuwata, Takumi |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Ferritin keeps cells from being damaged by reactive oxygen species produced by Fe2+ and storages the oxidized iron in its cavity as iron cores. The iron core contains a various amount of inorganic phosphate (Pi). In bacteria, the amount of phosphate is comparable to that of iron. In contrast, ferritins from mammals contain only a tenth phosphate. It is not clear how the phosphate works in the iron oxidation and mineralization process. In this research, I investigated the effect of the phosphate on the structural feature of iron cores formed in the cavity of Escherichia coli ferritin (EcFtnA) and on its function. First, the structure of iron cores was characterized using analytical ultracentrifugation, transmission electron microscopy and small-angle X-ray scattering. These experiments revealed that the iron core was a cluster of small particles of which diameter were 2-4 nm in the absence of phosphate whereas it had a hollow spherical structure of which the inner and outer diameters were 6 and 8 nm, respectively. The effects of phosphate on the oxidation/mineralization kinetics were also investigated spectrophotometrically. The oxidation reaction showed at least two kinetic phases when iron atoms beyond 72 Fe/protein shell were added. The initial phase corresponds to the binding of three irons to a ferroxidase center and subsequent oxidation, whereas the second one reflects the turnover, that is, the movement of oxidized iron from the ferroxidase center to the cavity. By comparing the kinetic curves with and without phosphates, it was revealed that the phosphate accelerated only the second phase, suggesting that the phosphate increases the turnover rate of the iron oxidation and/or mineralization process by EcFtnA. Neuroferritinopathy is a rare disease caused by mutations to human ferritin light chain gene (ftl1). While 9 of ten mutations reported to date produce ferritin mutants extended from 4 to 16 amino acid residues in the C-terminal region, A96T is a point mutant associated with neuroferritinopathy. The functional information of A96T has not been obtained in contrast to frameshift mutants. The iron incorporation activity of A96T mutant was investigated by native-PAGE using Prussian blue staining and change in absorbance intensity at 310nm. The result revealed that the iron incorporation activity of A96T is similar to that of human ferritin light chain wild type, and suggested that the pathogenic mechanism caused by A96T is different from the model proposed for frameshift mutants. |
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| 学位名 | ||||||
| 学位名 | 博士（理学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 創価大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2023-03-18 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第200号 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
